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BACKGROUND: Delayed treatment of congenital or infantile cataracts can cause deprivation amblyopia. Prompt diagnosis and surgical intervention is critical for optimal outcomes. This study assessed referral patterns for congenital or infantile cataracts in two regions of the United States. METHODS: The medical records of children 0-1 years of age with congenital or infantile cataracts at Stanford University (2008-2018) and Emory University (2010-2015) were reviewed retrospectively. RESULTS: A total of 111 children were included. Of these, 82 (74%) were initially evaluated by a primary care doctor, of whom 40 (49%) were referred directly to a pediatric cataract surgeon. Of 61 newborns 0-2 months of age, 9 (15%) were initially referred to an eye care provider before 6 weeks of age, but the initial evaluation by a pediatric cataract surgeon was delayed until after 6 weeks of age. Referral patterns were similar between the two institutions (P = 0.06). CONCLUSIONS: Many children with congenital of infantile cataracts are initially referred by a primary care doctor to an eye care provider who does not perform pediatric cataract surgery. Nevertheless, the majority of newborn infants with cataracts were evaluated by a pediatric cataract surgeon before 6 weeks of age.

Purpose To describe normative values for choroidal thickness in newborns and characterize their relationship to vitreoretinal features. Methods Term newborns underwent awake, handheld swept-source optical coherence tomography (SS-OCT) in this prospective cohort study. An automated segmentation algorithm followed by manual adjustments measured choroidal thickness at the fovea and five perifoveal locations. Two masked, trained graders, with a third mediating disagreements, analyzed scans for vitreoretinal findings. OCT vitreoretinal findings, including dome-shaped macula, subretinal fluid, punctate hyperreflective vitreous opacities, persistent inner retinal layers, foveal ellipsoid zone, tractional and non-tractional vitreous bands, epiretinal membrane, cystoid macular edema, vessel elevation, scalloped retinal layers, hyporeflective vessels, and retinal spaces, were assessed and correlated with foveal choroidal thickness using a generalized linear mixed model. Results Fifty-nine eyes of 39 infants (mean gestational age, 39.5 weeks; 18 male, 46%) were included. Mean foveal choroidal thickness was 455.5 ± 93.9 µm. Choroid was thinner inferonasally (343.6 ± 106.2 µm) compared to superonasally (368.4 ± 92.9 µm; P = 0.03) and superotemporally (369.6 ± 100.6 µm; P = 0.02). Thinner foveal choroidal thickness was associated with absence of a foveal ellipsoid zone (437.1 ± 78.5 µm vs. 553.7 ± 93.9 µm; P = 0.02). Choroidal thickness was not significantly associated with other OCT findings. Conclusions We identified an association between thinner choroid and foveal immaturity. Additional study is needed to determine whether choroidal development impacts visual outcomes. Translational Relevance Handheld SS-OCT achieved normative measurements for choroidal thickness across the macula in term newborns, providing a foundation for future investigations into the role of choroidal development in infancy.

Purpose: To describe a rare occurrence of acute vision loss and diffuse alveolar hemorrhage following a treatment of injectable gluteal cosmetic filler. Patient and methods: A 20-year-old female underwent a cosmetic injection of unknown components for gluteal augmentation. Within hours she developed progressive shortness of breath secondary to diffuse alveolar hemorrhage. She presented to ophthalmology 6 weeks later with a history of bilateral decreased vision. Clinical examination revealed cotton wool spots and retinal hemorrhages. Fluorescein angiography demonstrated macular vascular pruning and an enlarged foveal avascular zone. Results: The patient was observed and vision did not improve after 8 months of follow-up. Conclusion: These findings were attributed to a Purtscher-like retinopathy secondary to systemic inflammation induced by the filler and/or direct microembolization of the injected material or fat. To the best of the authors’ knowledge, this is the first documented case of diffuse alveolar hemorrhage and ischemic bilateral vision loss in a patient undergoing gluteal augmentation with dermal filler.

Central disruption of fusion refers to a subject's inability to fuse images, resulting in constant diplopia. Severely reduced vergences, or vergence anomalies, producing markedly decreased fusional amplitudes resembling fusional disruption have not been reported previously with convergence insufficiency. We report 3 patients with severe vergence anomalies in the setting of convergence insufficiency.

Purpose: We report a patient with severe multi-organ dysfunction of unknown origin who presented with bilateral orbital and chorioretinal manifestations that led to the diagnosis of Erdheim-Chester Disease (ECD). Observations: ECD is a rare, histiocytic, proliferative disorder characterized by multi-systemic organ involvement that has historically lacked effective therapy. Our patient underwent genetic testing that was positive for the BRAF V600E mutation; therefore, the patient was treated with vemurafenib. Conclusions and importance: This case demonstrates the rare orbital and intraocular manifestations of ECD and the unfortunate impact of a delayed diagnosis, the importance of early gene therapy testing for management decisions, and the utilization of targeted directed therapy to improve visual outcomes and quality of life. Keywords: Histiocytosis, Vemurafenib, Orbital, Chorioretinal, Xanthomatous, Lipogranulomatous, BRAF

Purpose To report the clinical features, antibiotic susceptibility profiles, treatment, and visual acuity (VA) outcomes of endophthalmitis caused by Corynebacterium species. Design Retrospective case series. Participants Patients with endophthalmitis caused by Corynebacterium species. Methods Microbiology database records were retrospectively reviewed for all patients with endophthalmitis caused by Corynebacterium species from January 1, 1990, to December 31, 2012, at a large university referral center. The corresponding clinical records were then reviewed to evaluate endophthalmitis clinical features and treatment outcomes. Main Outcome Measures Presenting clinical features, visual acuity outcomes, and antibiotic susceptibility patterns. Results For the 10 patients identified, clinical settings included post–cataract surgery (n = 6), post–penetrating keratoplasty (n = 2), and posttrabeculectomy (n = 2). The mean time from surgical procedure to presentation with endophthalmitis was 6.8 months (range: 1 day to 28 months). All isolates were susceptible to vancomycin. Presenting VA ranged from 7/200 to no light perception. Initial treatment strategies were vitreous tap and intravitreal antibiotic injection (n = 5) and pars plana vitrectomy with intravitreal antibiotic injection (n = 5). VA outcomes were ≥20/60 in 5 of 10 patients (50%) and ≤20/400 in 5 of 10 patients (50%). Conclusions The most common clinical setting was post–cataract surgery. All isolates were susceptible to vancomycin. Despite prompt treatment with appropriate antibiotics, visual outcomes varied.

To report the clinical settings, bacterial isolates, antibiotic sensitivities, and visual acuity outcomes of patients with persistently positive vitreous cultures after intravitreal antibiotics.Consecutive, noncomparative case series.setting: Tertiary care center.Thirty-six eyes of 36 patients with exogenous endophthalmitis with the same bacterial organism identified on at least 2 consecutive vitreous cultures from 1981 to 2015.Vitreous cultures with intravitreal injections of antibiotics and pars plana vitrectomies with intravitreal antibiotics.Bacterial isolates, antibiotic sensitivities, visual outcomes.Thirty-six eyes of 36 patients met the study criteria. The mean follow-up was 26.5 months. The most common clinical settings were after cataract extraction (18/36, 50%) and glaucoma surgery (11/36, 31%). The mean initial visual acuity was 2.16 ± 0.77 logMAR (Snellen equivalent ≈20/2900), and there was no statistically significant change at the final evaluation (2.08 ± 0.97 logMAR, ≈20/1900, P = .72). The most common bacteria were Staphylococcus (11/36, 31%) and Streptococcus (9/36, 25%). Gram-positive bacteria were sensitive to vancomycin (27/27, 100%); gram-negative bacteria were sensitive to amikacin (5/5, 100%). The antibiotic sensitivities were the same on repeat cultures in 34 of 36 patients (94%). The initial treatment was a vitreous culture and intravitreal injection of antibiotics in 28 of 36 patients (78%). The vision at the last follow-up was 20/200 or better in 12 patients (33%) and no light perception in 11 of 36 patients (31%).The most commonly identified organisms were gram-positive bacteria. There was good concordance in the antibiotic sensitivities between initial and subsequent cultures. Patients with persistently vitreous culture-positive endophthalmitis had poor visual outcomes.

To report the clinical features, antibiotic susceptibility profiles, treatment, and visual acuity (VA) outcomes of endophthalmitis caused byRetrospective case series.Patients with endophthalmitis caused byMicrobiology database records were retrospectively reviewed for all patients with endophthalmitis caused bypresenting clinical features, visual acuity outcomes, and antibiotic susceptibility patterns.Of 10 patients identified, clinical settings included post-cataract surgery (n = 6), post-penetrating keratoplasty (n = 2), and post-trabeculectomy (n = 2). The mean time from surgical procedure to presentation with endophthalmitis was 6.8 months (range: 1 day to 28 months). All isolates were vancomycin susceptible. Presenting VA ranged from 7/200 to no light perception. Initial treatment strategies were vitreous tap and intravitreal antibiotic injection (n = 5) and pars plana vitrectomy with intravitreal antibiotic injection (n = 5). VA outcomes were ≥ 20/60 in 5 (50%) of 10 patients and ≤ 20/400 in 5 (50%) of 10 patients.The most common clinical setting was post-cataract surgery. All isolates were susceptible to vancomycin. Despite prompt treatment with appropriate antibiotics, there were variable visual outcomes.

Background The aims of this study were to evaluate visual function outcomes in idiopathic intracranial hypertension (IIH) patients who underwent ventriculoperitoneal (VP) shunt for visual loss and to determine a VP shunt survival curve over time. Methods A retrospective medical record review was performed of all new IIH patients first evaluated at our institution who underwent VP shunt placement over a 7-year period (2004-2010). There were 2 primary outcome measures: the first being visual acuity (VA) and the second being shunt survival. Patients who received VP shunt for visual loss were included in the visual outcome analysis, and all patients who received VP shunt for any reason were included in the shunt survival analysis. Results Of the 338 new patients with IIH, 19 patients (6%) met the inclusion criteria and 17 underwent VP shunt for visual loss and 2 for headaches. Average follow-up was 21.2 months (range, 5-1,342 days). Of the 17 patients who had VP shunt for visual loss, 5 patients had optic nerve sheath fenestration (ONSF) surgery before VP shunt, and 1 patient had bilateral ONSF surgery after VP shunt. Median VA before shunt was 20/200 in the worse eye (range, 20/20 to NLP) and 20/40 in the better eye (20/20 to HM). Median VA after shunt was 20/60 in the worse eye (20/20 to lumboperitoneal) and 20/30 in the better eye (20/20 to 20/800). The improvement in VA was statistically significant in both worse eyes (P = 0.002, Wilcoxon signed-rank test) and better eyes (P = 0.028). The mean automated visual field (AVF) mean deviation (MD) of available AVFs before shunt was 223.36 dB (range, 233.38 to 27.01 dB) for the worse eye (n = 11) and 219.66 dB (230.11 to 25.91 dB) for the better eye (n = 11). Mean AVF MD deviation of available AVFs after shunt was 220.68 dB (232.13 to 23.97 dB) for the worse eye (n = 11) and 216.35 dB (232.13 to 21.00 dB) for the better eye (n = 11): this improvement was not significant (P = 0.27, P = 0.26, respectively). Independent masked record reviews by 3 neuro-ophthalmologists showed that 9 (53%) patients improved, 5 (29%) unchanged, 1 (6%) worsened, and 2 (12%) were indeterminate. Kaplan-Meier analysis showed a persistent steady decrease of functioning VP shunts over the entire period of 36 months with 80%, 65%, and 48% of VP shunts functioning without replacement, removal, or revision at 12, 24, and 36 months, respectively. Conclusion VP shunts improve or stabilize most IIH patients presenting with severe progressive visual loss or those with visual loss refractive to medical treatment and ONSF. Survival analysis shows persistent decrease of functioning shunts over time.

Purpose To develop an automated method of localizing and discerning multiple types of findings in retinal images using a limited set of training data without hard-coded feature extraction as a step toward generalizing these methods to rare disease detection in which a limited number of training data are available. Methods Two ophthalmologists verified 243 retinal images, labeling important subsections of the image to generate 1324 image patches containing either hemorrhages, microaneurysms, exudates, retinal neovascularization, or normal-appearing structures from the Kaggle dataset. These image patches were used to train one standard convolutional neural network to predict the presence of these five classes. A sliding window method was used to generate probability maps across the entire image. Results The method was validated on the eOphta dataset of 148 whole retinal images for microaneurysms and 47 for exudates. A pixel-wise classification of the area under the curve of the receiver operating characteristic of 0.94 and 0.95, as well as a lesion-wise area under the precision recall curve of 0.86 and 0.64, was achieved for microaneurysms and exudates, respectively. Conclusions Regionally trained convolutional neural networks can generate lesion-specific probability maps able to detect and distinguish between subtle pathologic lesions with only a few hundred training examples per lesion.

We report here the in vivo conversion of [3H]myoinositol to [3H]chiroinositol. After labeling intraperitoneally with [3H]myoinositol for 3 days to reach radioisotope equilibrium in urine, [3H]chiroinositol was isolated from tissues and purified after 6 N HCl hydrolysis by two sequential paper chromatographies and high performance liquid chromatography (HPLC). Percent conversion of [3H]myoinositol to [3H]chiroinositol was highest in urine (36%), liver (8.8%), muscle (8.8%), and blood (7.6%) with intestine, brain, kidney, spleen, and heart decreasing in percentage from 2.8 to 0.7%. Labeling of other inositol isomers including scyllo-, neo-, and epi-, and mucoinositol was minimal, approximately 0.06% of [3H]myoinositol. Glucose was unlabeled, but glucuronate, the product of myoinositol oxidation, was labeled up to 1.5% of the [3H] myoinositol. Acid hydrolysates of combined inositol-containing phospholipids contain significant labeled chiroinositol. [3H]Phosphatidylinositols and [3H]glycosylphosphatidylinositols were extracted from liver, muscle, and blood, isolated by thin layer chromatography, and inositols purified by HPLC after acid hydrolysis. Percent conversion of [3H]myoinositol to [3H] chiroinositol was highest in blood (60.4%) followed by muscle (7.7%) and liver (2.2%).

We compared the effects of infusing a chemically defined chiro-inositol glycan putative insulin mediator with an equivalent dose of insulin in low-dose (45 mg/kg) streptozotocin diabetic rats. Insulin decreased plasma glucose levels from 17.32 +/- 0.17 to 3.96 +/- 0.064 mmol/l (p < 0.0002) in 120 min, a decrease of 77.13%, while the putative mediator promoted a decrease in plasma glucose from 14.85 +/- 0.084 to 7.22 +/- 0.13 mmol/l (p < 0.007) in 60 min. The putative mediator maintained euglycaemia over the ensuing 60 min with a plasma glucose level of 7.01 +/- 0.10 mmol/l at 120 min. Thus, insulin further reduced the plasma glucose from euglycaemia at 60 min to produce hypoglycaemia at 120 min. The lack of production of hypoglycaemia by the putative mediator can be explained by its inhibition of glucose-stimulated insulin secretion by the islet beta cells, thus providing a potential negative feedback regulatory mechanism; or by its selective action on muscle to increase glycogen synthesis. The significance of these results in terms of future directions in drug design is herein considered.

We have studied the mechanism of generation of insulin mediators by using specific antibodies raised against the oligosaccharide anchor of membrane proteins. These antibodies (i) block the in vitro effects of purified insulin mediators and (ii) block the insulin-induced stimulation of pyruvate dehydrogenase in intact BC3H1 myocytes but not insulin-stimulated glucose uptake, generation of diacylglycerol, or generation of insulin mediators. When added to intact cells in the presence of insulin, these antibodies induce the accumulation of insulin mediator activity in the extracellular medium. We therefore conclude that these anti-inositolglycan antibodies block some of the effects of insulin by inhibiting the uptake of specific insulin mediators generated outside the cell.

It has been proposed that the active centre of cyclic AMP-dependent protein kinase contains an arginine-recognition site, which is considered to be essential for the function of the catalytic subunit of the kinase [Matsuo, Huang & Huang (1978) Biochem. J.173, 441–447]. The catalytic subunit can be inactivated by 3-(3-dimethylaminopropyl)-1-ethylcarbodi-imide and glycine ethyl ester at pH6.5. The enzyme can be protected from inactivation by preincubation with histone, a protein substrate of the enzyme. On the other hand, ATP, which also serves as a protein kinase substrate, does not afford protection. Polyarginine, a competitive inhibitor of protein kinase, which is known from kinetic studies to interact specifically with the arginine-recognition site, partially protects the catalytic subunit from inactivation by 3-(3-dimethylaminopropyl)-1-ethylcarbodi-imide. These results lead to the conclusion that the site of modification by carbodi-imide/glycine ethyl ester is most likely located at the arginine-recognition site of the active centre. A value of 1.7±0.2 (mean±s.d.) mol of carboxy groups per mol of catalytic subunit has been obtained for the number of essential carboxy groups for the function of protein kinase; a complete chemical modification of these essential carboxy groups results in total loss of catalytic activity. Finally, we have identified the essential carboxy group in the catalytic subunit of cyclic AMP-dependent protein kinase as being derived from glutamate residues. This is achieved by a three-step procedure involving an extensive proteolytic digestion of the [1-14C]glycine ethyl ester-modified enzyme and two successive high-voltage electrophoreses of the hydrolysate. It is concluded that 1.7mol of glutamyl carboxy groups per mol of catalytic subunit may be considered a component of the arginine-recognition site in the active centre of cyclic AMP-dependent protein kinase.

Substantial evidence suggests that insulin receptor-associated protein kinase may play a pivotal role in the expression of the intracellular effects of insulin. This study was undertaken to determine whether insulin receptor kinase contributes to the generation of putative insulin mediators. The effect of ATP and divalent cation addition on the production of insulin mediators from liver plasma membranes was investigated. ATP (1 mM) added to liver plasma membranes in the absence of divalent cations enhanced insulin-stimulated release/generation of mediator slightly (approximately 3-fold). ATP in the presence of Mn2+ further increased release/generation of mediator markedly (approximately 100-fold). In contrast, ATP in the presence of Mg2+ had no stimulatory effect. Mn2+ and Mg2+ alone were ineffective. Addition of EDTA completely diminished the stimulatory effects of insulin, ATP, and Mn2+. The stimulation was ATP-specific since other nucleotides and nonhydrolyzable analogues of ATP had no or very weak activity. ATP-Mn2+ stimulated insulin-dependent mediator release/generation in a dose-dependent manner. These results suggest that insulin mediator release/generation is markedly stimulated by an ATP-Mn2+-dependent phosphorylation reaction, similar to insulin-stimulated receptor tyrosine kinase phosphorylation.

The My-1 cell surface antigen is expressed on human granulocytes and granulocytic precursor cells. The sugar sequence which occurs in the glycolipid, lacto-N-fucopentaose III ceramide, in several higher glycolipids, and in glycoproteins, contains the epitope recognized by anti-My-1 and 17 other monoclonal antibodies with the same cellular specificity. Download : Download high-res image (12KB) Download : Download full-size image

Deproteinized skeletal muscle extracts free of major nucleotides from control and insulin-treated rats were fractionated and assayed for inhibition of protein phosphorylation by cyclic adenosine monophosphate (AMP)-dependent and -independent protein kinases. A differential effect of insulin on a particular fraction was observed on cyclic AMP-dependent protein kinase but not on cyclic AMP-independent protein kinases. This fraction that inhibited cyclic AMP-dependent protein kinase also stimulated glycogen synthase phosphoprotein phosphatase. It is proposed that this fraction may contain a mediator substance generateed in the presence of insulin.

On the basis of the chemical and structural features of the amino acid sequences in the vicinities of phosphorylatable hydroxyamino acid residues in several of the well-known protein substrates for skeletal-muscle cyclic AMP-dependent protein kinase, it is hypothesized that the phosphorylatable residue at position i and arginine residue at position i-3 of these protein substrates are located on a peptide turn on the hydrophilic protein surface. It is further hypothesized that there is an arginine-recognition site near the active centre on the protein kinase. This site is essential for the function of cyclic AMP-dependent protein kinase, for, not only does it recognize specifically the exposed arginine residue of the protein substrate, but, more importantly, via the interaction with arginine-(i′3), it may help to steer the topologically adjacent serine-i into proper orientation on the nearby active centre for phosphorylation. Model-building and kinetic data that provide support for the proposed hypotheses are presented.

SUMMARY Insulin treatment significantly altered the elution profile of deproteinized muscle extracts chromato-graphed on Sephadex G-25 columns, particularly in fraction II, which contains the insulin mediator. Further purification of fraction II by high-voltage paper electrophoresis at pH 1.9 and 3.5 resulted in two active fractions. Fraction 1 → 4 stimulated the cyclic AMP-dependent protein kinase and inhibited glycogen synthase phosphoprotein phosphatase, and may be a novel substance. Fractions 1 → > 6 and 3 → 6 inhibited the cyclic AMP-dependent protein kinase and stimulated glycogen synthase phosphatase. It is proposed that the insulin mediator is present in fractions 1 → 6 and 3 → 6.